Structural Properties of Polyglutamine Aggregates Investigated via Molecular Dynamics Simulations

Polyglutamine (polyQ) beta-stranded aggregates constitute the hallmark of Huntington disease. The disease is fully penetrant when Q residues are more than 36-40 ("disease threshold"). Here, based on a molecular dynamics study on polyQ helical structures of different shapes and oligomeric states, we suggest that the stability of the aggregates increases with the number of monomers, while it is rather insensitive to the number of Qs in each monomer. However, the stability of the single monomer does depend on the number of side-chain intramolecular H-bonds, and therefore oil the number of Qs. If such number is lower than that of the disease threshold, the beta-stranded monomers are unstable and hence may aggregate with lower probability, consistently with experimental findings. Our results provide a possible interpretation of the apparent polyQ length dependent-toxicity, and they do not support the so-called "structural threshold hypothesis", which supposes a transition from random coil to a beta-sheet structure only above the disease threshold

Inpatient Transfers to the Intensive Care Unit: Delays Are Associated With Increased Mortality and Morbidity

OBJECTIVE: To examine if delayed transfer to the intensive care unit (ICU) after physiologic deterioration is associated with increased morbidity and mortality. DESIGN: Inception cohort. SETTING: Community hospital in Ogden, Utah. PATIENTS: Ninety-one consecutive inpatients with noncardiac diagnoses at the time of emergent transfer to the ICU. We determined the time when each patient first met any of 11 pre-specified physiologic criteria. We classified patients as “slow transfer” when patients met a physiologic criterion 4 or more hours before transfer to the ICU. Patients were followed until discharge. INTERVENTIONS: None. MEASUREMENTS: In-hospital mortality, functional status at hospital discharge, hospital resources. MAIN RESULTS: At the time when the first physiologic criterion was met on the ward, slow- and rapid-transfer patients were similar in terms of age, gender, diagnosis, number of days in hospital prior to ICU transfer, prehospital functional status, and APACHE II scores. By the time slow-transfer patients were admitted to the ICU, they had significantly higher APACHE II scores (21.7 vs 16.2; P = .002) and were more likely to die in-hospital (41% vs 11%; relative risk [RR], 3.5; 95% confidence interval [95% CI], 1.4 to 9.5). Slow-transfer patients were less likely to have had their physician notified of deterioration within 2 hours of meeting physiologic criteria (59% vs 31%; P = .001) and less likely to have had a bedside physician evaluation within the first 3 hours after meeting criteria (23% vs 83%; P = .001). CONCLUSIONS: Slow transfer to the ICU of physiologically defined high-risk hospitalized patients was associated with increased risk of death. Slow response to physiologic deterioration may explain these findings

The effect of embedded managerial values on corporate financial outcomes

This paper explored the relationship between the embeddedness of a firm’s managerial values and corporate financial performance in Swiss small and medium-sized enterprises (SMEs) by developing a conceptual maturity model of managerial values (MM-MV). The MM-MV articulates the extent to which managerial values are embedded within organizations, allowing the analysis of the interrelationship between the degree of values-embeddedness and financial performance in SMEs. The findings suggested that as managerial values become more embedded, financial performance increases; therefore, SMEs exhibiting highly embedded managerial values such as customer-minded, team spirit, innovation-driven reliability, persis-tency, competency, and engagement tend to financially outperform SMEs that have not fully embedded managerial values throughout the firm